Effects of a water-soluble formulation of tylvalosin on disease caused by porcine reproductive and respiratory syndrome virus alone in sows or in combination with Mycoplasma hyopneumoniae in piglets.

BACKGROUND: The effect of a water-soluble formulation of tylvalosin (Aivlosin® 625 mg/g granules) on disease caused by porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (Mhyop) was investigated in two animal studies. In a PRRSV challenge model in pregnant sows (n = 18), six sows received water medicated at target dose of 5 mg tylvalosin/kg body weight/day from 3 days prior to challenge until the end of gestation. Six sows were left untreated, with a third group remaining untreated and unchallenged. Sows were challenged with PRRSV-2 at approximately 85 days of gestation. Cytokines, viremia, viral shedding, sow reproductive parameters and piglet performance to weaning were evaluated. In a dual infection study (n = 16), piglets were challenged with Mhyop on days 0, 1 and 2, and with PRRSV-1 on day 14 and euthanized on day 24. From day 10 to 20, eight piglets received water medicated at target dose of 20 mg tylvalosin/kg body weight/day and eight piglets were left untreated. Cytokines, viremia, bacteriology and lung lesions were evaluated. RESULTS: In the PRRSV challenge study in pregnant sows, tylvalosin significantly reduced the levels of serum IL-8 (P < 0.001), IL-12 (P = 0.032), TNFα (P < 0.001) and GM-CSF (P = 0.001). IL-8 (P = 0.100) tended to be lower in uterus of tylvalosin sows. All piglets from tylvalosin sows surviving to weaning were PRRSV negative in faecal swabs at weaning compared to 33.3% PRRSV positive piglets from untreated sows (P = 0.08). In the dual challenge study in piglet, tylvalosin reduced serum IL1ß, IL-4, IL-6, IL-8, IL-10, IL-12, IL-1α, IL-13, IL-17A, IL-18, GM-CSF, TGFß1, TNFα, CCL3L1, MIG, PEPCAM-1 (P < 0.001) and increased serum IFNα, IL-1ra and MIP-1b (P < 0.001). In the lungs, tylvalosin reduced IL-8, IL-10 and IL-12 compared to untreated pigs (P < 0.001) and tended to reduce TNFα (P = 0.082). Lung lavage samples from all tylvalosin treated piglets were negative for Mhyop (0 cfu/mL) compared to the untreated piglets which had mean Mhyop counts of 2.68 × 104 cfu/mL (P = 0.023). CONCLUSION: Overall, tylvalosin reduced both local and systemic proinflammatory cytokines after challenge with respiratory pathogens in sows and in piglets. Tylvalosin was effective in reducing Mhyop recovery from the lungs and may reduce virus shedding in piglets following transplacental PRRSV infection in sows.

Efficacy of oleandrin and PBI-05204 against bovine viruses of importance to commercial cattle health.

BACKGROUND: Bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV). and bovine coronavirus (BCV) threaten the productivity of cattle worldwide. Development of therapeutics that can control the spread of these viruses is an unmet need. The present research was designed to explore the in vitro antiviral activity of the Nerium oleander derived cardiac glycoside oleandrin and a defined N. oleander plant extract (PBI-05204) containing oleandrin. METHODS: Madin Darby Bovine Kidney (MDBK) cells, Bovine Turbinate (BT) cells, and Human Rectal Tumor-18 (HRT-18) cells were used as in vitro culture systems for BVDV, BRSV and BCV, respectively. Cytotoxicity was established using serial dilutions of oleandrin or PBI-05204. Noncytotoxic concentrations of each drug were used either prior to or at 12 h and 24 h following virus exposure to corresponding viruses. Infectious virus titers were determined following each treatment. RESULTS: Both oleandrin as well as PBI-05204 demonstrated strong antiviral activity against BVDV, BRSV, and BCV, in a dose-dependent manner, when added prior to or following infection of host cells. Determination of viral loads by PCR demonstrated a concentration dependent decline in virus replication. Importantly, the relative ability of virus produced from treated cultures to infect new host cells was reduced by as much as 10,000-fold at noncytotoxic concentrations of oleandrin or PBI-05204. CONCLUSIONS: The research demonstrates the potency of oleandrin and PBI-05204 to inhibit infectivity of three important enveloped bovine viruses in vitro. These data showing non-toxic concentrations of oleandrin inhibiting infectivity of three bovine viruses support further investigation of in vivo antiviral efficacy.

The effects of vaccination on serum hormone concentrations and conception rates in synchronized naive beef heifers.

Crossbred beef heifers (N = 59) were vaccinated at the time of synchronization/breeding with either a commercially available bovine herpesvirus type 1 modified live virus (MLV) (one dose) or inactivated virus vaccine (one or two doses). The estrus cycle was synchronized at vaccination and heifers were artificially inseminated 8 days (one dose) or 36 days (two dose) after initial vaccination. Pregnancy rates were greater for control heifers (90%; P = 0.02) and heifers given the inactivated virus vaccine (one dose: 86%; P = 0.08; or two: 90%; P < 0.01) than those given the MLV vaccine (48%). No control heifers experienced an abnormal estrous cycle, whereas only two (two dose; 2/21) and one (one dose; 1/7) heifers in the inactive virus groups had abnormal estrous cycles and were similar to control (P > 0.10). Heifers given the MLV vaccine had a greater (P = 0.02) percentage of abnormal estrous cycles (38%; 8/21) compared with the control and inactivated groups. Of the heifers with an abnormal estrous cycle, 100% of heifers given the inactivated vaccine (one or two dose) conceived at their return estrus, whereas only 38% of heifers given the MLV vaccine conceived at their return estrus (P > 0.10). During the synchronization period, concentrations of estrogen were greater (P < 0.01) in the control and the two-dose inactivated group compared with the MLV group. After AI, progesterone concentrations were greater (P < 0.01) in control heifers compared with the inactivated and MLV groups, but were similar (P ≥ 0.18) between the inactivated and MLV groups. Therefore, naïve heifers vaccinated with the inactivated vaccine were less likely to have an abnormal estrous cycle and had significantly higher pregnancy rates compared with heifers vaccinated with the MLV vaccine. In summary, vaccination of naïve heifers with an MLV vaccine at the start of a fixed-time AI protocol had a negative effect on pregnancy success.